Description: (Applicant's Description) Patients with second primary tumors (SPTs), a hallmark of upper aerodigestive tract cancers, may have different epidemiologic exposure profiles and may be more likely to exhibit susceptible genotypes than patients with a single primary. We propose to evaluate a panel of markers of susceptibility in the patients enrolled in Dr. W. K. Hong?s Chemoprevention Project (Project 1) as predictors of second tumor risk. This research builds upon the clinical, epidemiologic, and cytogenetic data derived from the parent program project and also utilizes a case-control study design nested in the cohort of patients established in the parent chemoprevention trial and to be continued in the ongoing proposal. The first two specific aims are a continuation of the original proposal and three new aims are added. Specifically, we propose: 1. To continue the collection of the epidemiologic profiles of cases (patients with SPTs) and controls (patients without SPTs). 2. To continue the collection of dietary intake data from patients enrolled in Project 1, specifically, data regarding carotenoid and antioxidant intake to test the hypothesis that decreased intake of these micronutrients may be associated with increased risk for SPTs. 3. To compare the genotype frequencies of several metabolic genes including CYP1Al, CYP2D6, GSTM1, GSTT1, epoxide hydrolase, and N-acetyltransferase polymorphisms in all patients. The data from these three specific aims will be used to construct a quantitative risk assessment model to predict risk of SPT. The identification of subgroups of patients with upper aerodigestive tract cancers who are at increased risk for SPT has both clinical and prognostic relevance. High risk patients can be targeted for intensive primary and secondary preventive strategies and can be enrolled into chemoprevention trials.